Chemosensitivity

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity, Volume 1: In Vitro Assays provides a panel of 16 in vitro measures of chemosensitivity in adherent and non-adherent cells for single agents and combinations of agents. In addition to immunohistochemical and imaging approaches, these assays include clonogenic, colorimetric, fluorometric, and physiological assays. Highlights include image analysis to assess drug sensitivity, high throughput approaches using green fluorescent protein, DIMSCAN (a microcomputer fluorescence-based assay), and the ChemoFx assay used in biotechnology. A companion volume, Volume 2: In Vivo Models, Imaging, and Molecular Regulators, provides protocols for classifying tumors into response categories and customizing chemotherapy regimens to individual patients.

Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.

In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem, the book then focuses on the latest findings of molecular mechanisms of drug resistance. Coverage provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment. It allows those who are interested in breast cancer therapy to get a jump-start on critical issues in breast cancer therapeutic resistance.

The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis that the carotid body is also a physiological glucosensor, with a role in mediating exercise hyperpnoea. In anaesthetised rats, insulin-induced hypoglycaemia (from ca. 6.5 to 2.8 mmol L-1) caused an ca. two-fold increase of oxygen consumption that was associated with a significant, carotid body-dependent increase in ventilation (from ca. 420 to 640 ml min-1 kg-1) without change in blood gas tensions. This hypoglycaemic hyperpnoea was associated with hypokalaemia and no alterations of ventilation or metabolism were observed in euglycaemic, control studies, thus excluding any role for [K+] or insulin. During hypermetabolism, a proportional augmentation of peripheral CO2 gain, measured from the phrenic electroneurogram during artificial ventilation, was shown to maintain the arterial blood gas status. In vitro, measurements of single-fibre chemoafferent discharge showed that low [glucose], over a physiological range and during normoxia, increased neither the carotid baseline discharge nor the CO2 sensitivity. Taken together, these results demonstrate that the carotid body is not a physiological sensor of glucose but augmentation of the carotid body chemosensitivity via an undetermined yet, hypermetabolism-related factor(s) is most likely to be involved in exercise hyperpnoea.

'It will form an important addition to a scientific library and a useful addition to the (contributions series) which should be part of any obstetrics and gynaecology library.' New Zealand Journal of Obstetrics and Gynaecology

Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.

"PH and Brain Function offers thorough coverage of this increasingly important area of research, beginning with the fundamental concepts, which include methodological and theoretical issues such as the measurement of pH and the concept of pH in neurobiology. It explores aspects of regulation and modulation of intracellular pH in brain cells, surveys the changes in pH that occur with neural activity and how these changes affect neural activity, and discusses the role of pH in the pathophysiology of neurological diseases." "pH and Brain Function is an important resource for researchers in all areas of neuroscience as well as cell biology and physiology." --Book Jacket.